The Efficacy and Safety of Vardenafil in the Treatment of Pulmonary Arterial Hypertension

NCT ID: NCT00718952

Last Updated: 2010-02-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-07-31
• Study Completion Date: 2010-02-28

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of vardenafil in the treatment of pulmonary arterial hypertension.

Detailed Description

Pulmonary arterial hypertension (PAH), defined as a mean pulmonary artery pressure ≥25 mmHg with a pulmonary capillary wedge pressure ≤15 mmHg measured by cardiac catheterization, is a disorder that may occur either in the setting of a variety of underlying medical conditions or as a disease that uniquely affects the pulmonary circulation. Irrespective of its etiologies, PAH is a serious and often progressive disorder that results in right ventricular dysfunction and impairment in activity tolerance, and may lead to right-heart failure and death. The pathogenesis of PAH is complex and incompletely understood, but includes both genetic and environmental factors that alter vascular structure and function.

In recent years, several new drugs have been developed for the treatment of pulmonary arterial hypertension (PAH), including continuous intravenous epoprostenol, inhaled iloprost, subcutaneous trepostinil, oral bosentan, and oral beraprost. In addition, there is increasing evidence for the therapeutic effectiveness of the phosphodiesterase-5 (PDE-5) inhibitor sildenafil in PAH. Phosphodiesterases are a superfamily of enzymes that inactivate cyclic adenosine monophosphate and cyclic guanosine monophosphate, the second messengers of prostacyclin and nitric oxide (NO) .The phosphodiesterases have different tissue distributions and substrate affinities. Interestingly, PDE-5 is abundantly expressed in lung tissue, thus offering as target molecule for PAH treatment concepts.

The three commercially available PDE-5 inhibitors (sildenafil, vardenafil, and tadalafil) are currently approved for the treatment of erectile dysfunction . These inhibitors are now receiving attention for their activity in the pulmonary vasculature. Sildenafil has been proved to improve the exercise capacity and pulmonary hemodynamics of PAH patients, however, there are few reports regarding the use of vardenafil or tadalafil on the pulmonary vasculature. Although sildenafil, vardenafil, and tadalafil act on the same enzyme, these drugs exhibit different pharmacokinetics and selectivity, and therefore may not be equally efficacious in the pulmonary vascular bed. As vardenafil has a more than 20-fold greater potency than sildenafil for inhibiting purified PDE-5, we assume that it will show more favorable clinical and side-effect profiles in treating PAH.

This is a prospective, randomized, placebo-controlled, pilot study to evaluate the efficacy and safety of vardenafil in the treatment of pulmonary arterial hypertension.

Conditions

Pulmonary Hypertension

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

A

Patients in group A will receive vardenafil in double-blinded treatment period.

Group Type: EXPERIMENTAL

Vardenafil

Intervention Type: DRUG

vardenafil tablet 5mg once-daily orally in the first 4 weeks while 5mg twice-daily orally in the following 8 weeks.

Vardenafil

Intervention Type: DRUG

Patients in all the 2 arms will take vardenafil tablet 5mg twice-daily orally from week 13 to week 24(open-label).

B

Patients in group A will receive placebo in double-blinded treatment period.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo tablet 5mg once-daily orally in the first 4 weeks while 5mg twice-daily orally in the following 8 weeks.

Vardenafil

Intervention Type: DRUG

Patients in all the 2 arms will take vardenafil tablet 5mg twice-daily orally from week 13 to week 24(open-label).

Interventions

Vardenafil

vardenafil tablet 5mg once-daily orally in the first 4 weeks while 5mg twice-daily orally in the following 8 weeks.

Intervention Type: DRUG

Placebo

Placebo tablet 5mg once-daily orally in the first 4 weeks while 5mg twice-daily orally in the following 8 weeks.

Intervention Type: DRUG

Vardenafil

Patients in all the 2 arms will take vardenafil tablet 5mg twice-daily orally from week 13 to week 24(open-label).

Intervention Type: DRUG

Other Intervention Names

Levitra; Levitra

Eligibility Criteria

Inclusion Criteria

• Subjects aged 12-65.
• Confirmed idiopathic pulmonary hypertension, connective tissue disease associated pulmonary hypertension, congenital heart disease(with Eisenmenger syndrome) associated pulmonary hypertension.
• Baseline 6-minutes walking distance 150m-550m.
• WHO pulmonary hypertension function II-III with non-responder to calcium channel blockers.
• Documented written informed consent.

Exclusion Criteria

• The other types of pulmonary hypertension.
• Subjects who refuse to subscribe written informed consents or can't cooperate with the trial well.
• Subjects with serious acute or chronic disease involved liver, kidney, and brain or have to use potent CYP3A4-inhibitor or nitrate to treat the underlying diseases.
• Subjects who are currently treated with sildenafil for PAH or taking sildenafil or tadalafil.
• Other contraindications in package insert.

• Minimum Eligible Age: 12 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Tongji University

OTHER

Sponsor Role: lead

Responsible Party

Shanghai Pulmonary Hospital, Tongji University,Shanghai, China

Principal Investigators

Zhi-Cheng Jing, MD

Role: PRINCIPAL_INVESTIGATOR

Shanghai Pulmonary Hospital Affiliated to Tongji University, Shanghai, China

Locations

Peking University First Hospital

Beijing, Beijing Municipality, China

Peking University First Hospital

Beijing, Beijing Municipality, China

Peking Union Hospital, Peking Union Medical College

Beijing, Beijing Municipality, China

Beijing Shijitan Hospital, Peking University

Beijing, Beijing Municipality, China

The First Clinical College of Harbin Medical University

Harbin, Heilongjiang, China

Xiangya Hospital, Central-South University

Changsha, Hunan, China

The General Hospital of Shenyang Military Command

Shenyang, Liaoning, China

Renji Hospital, Shanghai Jiaotong University

Shanghai, Shanghai Municipality, China

The First Affiliated Hospital of Medical College of Xian Jiaotong University

Xi’an, Shanxi, China

Shanghai Pulmonary Hospital ,Tongji University

Shanghai, , China

Countries

China

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Other Identifiers

EVALUATION-01

Identifier Type: -

Identifier Source: org_study_id